Immunoproteomics to identify species-specific antigens in Neospora caninum recognised by infected bovine sera

Bovine neosporosis is a disease of concern due to its global distribution and significant economic impact through massive losses in the dairy and meat industries. To date, there is no effective chemotherapeutic drug or vaccine to prevent neosporosis. Control of this disease is therefore dependent on efficient detection tests that may affect treatment management strategies. This study was conducted to identify the specific immunoreactive proteins of Neospora caninum tachyzoites recognised by sera from cattle infected with N. caninum, Toxoplasma gondii, Cryptosporidium parvum, Babesia bovis and B. bigemina, and by sera from uninfected cattle using two-DE dimensional gel electrophoresis (2-DE) combined with immunoblot and mass spectrometry (LC-MS/MS). Among 70 protein spots that reacted with all infected sera, 20 specific antigenic spots corresponding to 14 different antigenic proteins were recognised by N. caninum-positive sera. Of these immunoreactive antigens, proteins involved in cell proliferation and invasion process were highly immunogenic, including HSP90-like protein, putative microneme 4 (MIC4), actin, elongation factor 1-alpha and armadillo/beta-catenin-like repeat-containing protein. Interestingly, we discovered an unnamed protein product, rhoptry protein (ROP1), possessing strong immunoreactivity against N. caninum but with no data on function available. Moreover, we identified cross-reactive antigens among these apicomplexan parasites, especially N. caninum, T. gondii and C. parvum. Neospora caninum-specific immunodominant proteins were identified for immunodiagnosis and vaccine development. The cross-reactive antigens could be evaluated as potential common vaccine candidates or drug targets to control the diseases caused by these apicomplexan protozoan parasites

Molecular Detection and Genetic Diversity of Tick-Borne Pathogens in Goats from the Southern Part of Thailand

Tick-borne hemoprotozoan and rickettsial diseases affect the health and productivity of small ruminants in tropical and subtropical regions. Despite the large population of goats in the southern part of Thailand, there is limited information on the prevalence of tick-borne pathogens. In this study, polymerase chain reaction was used to detect the presence of Theileria spp., T. ovis, T. orientalis, Babesia ovis, Anaplasma ovis, and A. marginale in 262 goats from three provinces in the southern part of Thailand. In this investigation, Theileria spp. and A. ovis were detected while T. ovis, B. ovis, and A. marginale were not detected. Overall infection rates of Theileria spp. and A. ovis were 10.3% and 1.5%, respectively. The co-infections of two parasites was observed in 1.5% of goats. Sequence analysis showed the presence of T. luwenshuni and T. orientalis in the goat samples. This study is the first to use the molecular detection of T. orientalis in Thai goats, and presents genetic characterization using the major piroplasm surface protein (MPSP) gene. In the phylogenetic analysis, the T. orientalis MPSP sequence was classified as type 7. The A. ovis major surface protein 4 (MSP4) gene sequences shared high identities and similarity with each other and clustered with isolates from other regions. This study provides information about the prevalence and genetic diversity of tick-borne pathogens in goats in the study area, and is expected to be valuable for the development of effective control measures to prevent disease in animals in Thailand

A Systematic Review and Meta-Analysis Exploring Variations in Copper Levels between Individuals with Malaria and Uninfected Controls

Micronutrient insufficiency has been implicated in malaria pathogenesis. However, the role of copper in malaria remains inconclusive. This study aimed to investigate the association between copper levels and malaria pathogenesis, providing a deeper understanding of copper’s role in the disease. A systematic review was conducted following the registered protocol in PROSPERO (CRD42023439732). Multiple databases, including Embase, MEDLINE, Ovid, PubMed, Scopus, and Google Scholar, were searched for relevant studies reporting blood copper levels in patients with malaria. The Joanna Briggs Institute critical appraisal checklist was used for assessing methodological quality. Qualitative and quantitative syntheses were employed, organizing, and summarizing the findings of the included studies. To calculate the standardized mean difference (Hedge’s g) and 95% confidence intervals (CIs), a random-effects model was used. After screening the databases, 16 studies were included. Most studies (52.9%) reported that individuals with malaria had significantly higher copper levels than uninfected controls. The meta-analysis, based on 16 studies, showed no significant difference in copper levels between patients with malaria and uninfected controls overall (p = 0.39; Hedges’ g, 0.38; 95% CI, −0.48 to 1.25; I2, 98.73%). Subgroup analysis showed a significant difference in copper levels between patients with malaria and uninfected controls among studies conducted in Asia (p I2, 90.88%; five studies) and studies employing plasma blood samples (p I2, 93.11%; four studies). The qualitative synthesis of the reviewed studies suggests a complex relationship between copper levels and malaria. The meta-analysis results showed no significant difference in copper levels between patients with malaria and uninfected controls overall. However, subgroup analyses based on various factors, including continent and blood sample type, showed copper level variations. These findings highlight the need for further research to better understand the role of copper in malaria pathogenesis by considering geographical factors and the blood sample type used for copper level measurement

Procalcitonin as a Candidate Biomarker for Malarial Infection and Severe Malaria: A Meta-Analysis

Procalcitonin (PCT), as a marker of malaria severity, remains to be investigated. The present study collated and compared the levels of PCT between patients with severe malaria, uncomplicated malaria, and control participants to assess their role in predicting malaria infection and disease severity. The systematic review was registered at PROSPERO with registration number CRD42021297243. The search for relevant studies that reported PCT in patients with malaria was performed in PubMed, Scopus, and Web of Science. The following meta-analyses were conducted; (1) the pooled mean PCT levels in patients with severe and uncomplicated malaria, and (2) the pooled mean difference in PCT levels between patients with severe and uncomplicated malaria. Fifteen studies were included for qualitative and quantitative syntheses. The meta-analysis results show that the pooled mean PCT levels in patients with uncomplicated malaria were 3.92 ng/mL (95% CI: 2.26–5.58 ng/mL, I2: 96.5, five studies), whereas the pooled mean PCT levels in patients with severe malaria were 14.13 ng/mL (95% CI: 8.75–19.5 ng/mL, I2: 92.6, six studies). The meta-analysis showed that patients with severe malaria had an equal mean of PCT compared to those with uncomplicated malaria when the random-effects model was used (p: 0.055, weighted mean difference: 6.93, 95% CI: −0.16–14.02, I2: 84.6%, four studies). There were probable correlations between the level of parasitemia, immunity level, and possibly bacterial or other parasitic co-infection that could affect the PCT level among different clinical severities of malaria. Therefore, the PCT level alone does not seem to be a suitable biomarker to discriminate the severe/uncomplicated or infected/uninfected cases. Further studies should investigate the increased PCT levels in combination with other markers in association with malaria infection and severity

Association between ovalocytosis and Plasmodium infection: a systematic review and meta-analysis

Abstract Reports of an association between ovalocytosis and protection against Plasmodium infection are inconsistent. Therefore, we aimed to synthesise the overall evidence of the association between ovalocytosis and malaria infection using a meta-analysis approach. The systematic review protocol was registered with PROSPERO (CRD42023393778). A systematic literature search of the MEDLINE, Embase, Scopus, PubMed, Ovid, and ProQuest databases, from inception to 30 December 2022, was performed to retrieve studies documenting the association between ovalocytosis and Plasmodium infection. The quality of the included studies was assessed using the Newcastle–Ottawa Scale. Data synthesis included a narrative synthesis and a meta-analysis to calculate the pooled effect estimate (log odds ratios [ORs]) and 95% confidence intervals (CIs) using the random-effects model. Our database search retrieved 905 articles, 16 of which were included for data synthesis. Qualitative synthesis revealed that over half of the studies showed no association between ovalocytosis and malaria infections or severity. Furthermore, our meta-analysis demonstrated no association between ovalocytosis and Plasmodium infection (P = 0.81, log OR = 0.06, 95% CI − 0.44 to 0.19, I2: 86.20%; 11 studies). In conclusion, the meta-analysis results demonstrated no association between ovalocytosis and Plasmodium infection. Hence, the role of ovalocytosis in relation to protection against Plasmodium infection or disease severity should be further investigated in larger prospective studies

Impact of malaria on glutathione peroxidase levels: a systematic review and meta-analysis

Abstract The primary antioxidant, glutathione peroxidase (GPx), is hypothesized to contribute to the pathophysiology of malaria. This current study conducted a meta-analysis to examine variations in GPx blood levels in malaria patients. Seven electronic databases—ProQuest, Scopus, Embase, MEDLINE, PubMed, Ovid, and Google Scholar—were searched for relevant studies with no limitations to publication language or publication date. The Joanna Briggs Institute critical appraisal tools were used to appraise the risk of bias among the included studies critically. The meta-analysis was conducted by pooling the effect estimates and Hedges’s g using a random-effects model. Search results returned 1253 articles, of which 16 studies were used for syntheses. Results of the meta-analysis indicated that malaria patients had decreased blood levels of GPx compared to uninfected individuals (P < 0.01, Hedges’ g: − 4.06, 95% CI − 5.49–(− 2.63), I 2: 99.07%, 1278 malaria patients/627 uninfected individuals, 15 studies). Subgroup analyses indicated that peripheral levels of GPx were significantly diminished in patients with P. falciparum malaria compared to uninfected controls (P < 0.01, Hedges’ g: − 3.06, 95% CI − 4.46–(− 1.65), I 2: 98.39%, 9 studies) but not in patients with P. vivax malaria (P = 0.15, Hedges’ g: − 2.05, 95% CI − 4.83–0.74), I 2: 98.64%, 2 studies) Overall, malaria is associated with declined levels of GPx, particularly in patients with P. falciparum malaria. The finding provides valuable insights that prompt the need to investigate the role of GPx depletion in malaria pathogenesis

Zoonotic potential of

Enterocytozoon bieneusi is a common opportunistic intestinal pathogen worldwide. Genotype distribution of E. bieneusi differs by geography and host immunity. In order to investigate the prevalence, genotype characteristics, and host specificity of E. bieneusi in the community, we conducted a preliminary cross-sectional study among children in Western and Northern Thailand. Seventy-eight (78) and 102 stool samples were collected; the prevalence of E. bieneusi was 3.8% and 2.9% by nested PCR in Western and Northern Thailand, respectively. Three genotypes were identified: Genotype D predominated, followed by EbpC, and then novel genotype ETMK1. The first two genotypes have zoonotic potential. Analysis of the genetic proximity of the E. bieneusi ITS sequences from our study, compared with those published in genetic databases, showed that all positive samples were classified into Group 1, the largest group consisting of various host specificity. The present study demonstrates the possible zoonotic transmission of E. bieneusi in rural communities in Thailand. A large-scale investigation of both human and animal samples, as well as improvements in the available phylogenetic tools, will be required to elucidate transmission routes of E. bieneusi in this area

Differences in catalase levels between malaria-infected individuals and uninfected controls: a systematic review and meta-analysis

Abstract Inconsistent catalase (CAT) research necessitates a comprehensive review of CAT levels among patients with malaria to achieve better therapeutic strategies. This study aimed to systematically review and meta-analyze available literature on CAT levels in nonpregnant and pregnant individuals with malaria compared with those in uninfected controls, with the goal of providing a robust evidence base for future research and potential interventions. Following PRISMA guidelines, a systematic literature search across six databases was conducted to examine CAT levels in patients with malaria. Data was extracted independently by two reviewers, and study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist. The standardized mean difference of CAT levels was calculated with heterogeneity assessment. Subgroup and sensitivity analyses were conducted to explore heterogeneity and assess the robustness of the findings. Publication bias was visually and statistically assessed and corrected, if necessary. Statistical analyses were performed using Stata software, with a significance level set at P < 0.05. Nineteen studies were included in the review. These studies, published from before 2000 to 2023, primarily from Africa and Asia, focused on different Plasmodium species and age groups. Results of qualitative synthesis among nonpregnant individuals consistently showed lower CAT levels in malaria-infected individuals, although some studies reported higher levels. No significant differences in CAT levels were found between malaria-infected and uninfected individuals, as demonstrated by a meta-analysis overall (P = 0.05, Hedges’ g: − 0.78, 95% confidence interval (CI): (− 1.56)–0.01, I2: 98.47, 15 studies), but subgroup analyses showed significant differences in CAT levels in studies conducted in Africa (P = 0.02, Hedges’ g: − 0.57, 95% CI: − 1.02–(0.11), I2: 91.81, 7 studies), and in studies that specifically focused on children (P = 0.03, Hedges’ g: − 0.57, 95% CI: − 1.07–(− 0.07), I2: 87.52, 4 studies). Pregnant women showed variations in CAT levels across trimesters. This study provides valuable insights into the association between malaria infection and CAT enzyme levels, particularly in nonpregnant individuals. Furthermore, well-designed studies are essential to decoding the intricacies of this relationship, which could have significant implications for understanding disease processes and improving patient care

Increased Blood Concentrations of Malondialdehyde in <i>Plasmodium</i> Infection: A Systematic Review and Meta-Analysis

Several studies have evaluated the relationship between malondialdehyde (MDA) concentrations and Plasmodium infections; however, the findings remain inconclusive. This study synthesized differences in MDA concentrations among patients with different levels of clinical severity, uninfected controls, and different Plasmodium species. The research protocol was registered in PROSPERO (CRD42023393540). Systematic literature searches for relevant studies were performed using the Embase, MEDLINE, Ovid, ProQuest, PubMed, Scopus, and Google Scholar databases. Qualitative and quantitative syntheses (meta-analyses) of distinct MDA concentrations between the disease groups were performed. Twenty-three studies met the eligibility criteria and were included in the systematic review. Overall, MDA concentrations were significantly elevated in participants with malaria relative to uninfected controls (p 2: 96.22%, 14 studies). Increased MDA concentrations in participants with malaria compared with uninfected controls were found in studies that enrolled patients with P. falciparum malaria (p 2: 89.7%, 7 studies) and P. vivax malaria (p 2: 90.11%, 3 studies). Our findings confirm that MDA concentrations increase during Plasmodium infection, indicating a rise in oxidative stress and lipid peroxidation. Thus, MDA levels can be a valuable biomarker for evaluating these processes in individuals with malaria. However, further research is necessary to fully elucidate the intricate relationship between malaria, antioxidants, oxidative stress, and the specific role of MDA in the progression of malaria